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Impact of Sample Handling and Processing on Bioanalycial Outcome

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Data from clinical assays (biomarkers, PK, PD, and immunogenicity) are often key outcomes from clinical trials. Implementing these endpoints in clinical trials is very costly and also time - and resource-consuming. Therefore, ensuring that appropriate measures are taken from the collection of samples until the completion of laboratory testing is paramount.

The purpose of this presentation is to discuss the challenges and potential pitfalls of sample collection, processing, and storage on the final bioanalytical endpoints and laboratory assays. Key parameters affecting various assay endpoints will be discussed and illustrated with specific examples, highlighting the SGS approach to handling and controlling these critical activities for the successful delivery of these studies outcomes.

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Impact of Sample Handling and Processing on Bioanalycial Outcome

  1. 1. IMPACT OF SAMPLE HANDLING AND PROCESSING ON BIOANALYTICAL OUTCOME Haiko Pillu Head Technical Operations CPU Antwerpen SAFETY & EFFICACY CLINICAL TRIAL SOLUTIONS SGS Life Science Services Biopharm Day Seminar – Antwerp, October 29, 2015
  2. 2. 2 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015 INTRODUCTION  Data from clinical assays (biomarkers, PK, PD, and immunogenicity) are often key outcomes from clinical trials  Implementing these endpoints in clinical trials is very :  Costly  time - and resource-consuming Ensuring appropriate measures are taken from the sample collection until the completion of laboratory testing is paramount.
  3. 3. 3 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015 SAMPLES WITHIN CLINICAL TRIALS Past  Clinical studies  sample treatments  PK samples  Low amount of PD samples  Sample treatment  1 step handling  Amount of time per sample = limited  Techniques  Centrifugation  Aliquoting  Freezing  Occasional sample preparations with larger sample treatments/procedures Present  Clinical studies  larger/ expanded sample treatments  PK assesments  PD assesments : more specific treatments on sample preparation  Sample treatments  Multiple steps during treatments  sample treatments up to 5h for each sample /batch of samples  Large amount of samples/aliquots  up to 10 different assays on 1 time point  Specific conditions  Time consuming treatment schedules  New processes  new techniques  Implementation new techniques  Need for training, specific qualifications  Running pilot studies evolution
  4. 4. 4 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015 SAMPLES WITHIN CLINICAL TRIALS Past  Clinical studies  sample treatments  PK samples  Low amount of PD samples  Sample treatment  1 step handling  Amount of time per sample = limited  Techniques  Centrifugation  Aliquoting  Freezing  Occasional sample preparations with larger sample treatments/procedures Present  Clinical studies  larger/ expanded sample treatments  PK assesments  PD assesments : more specific treatments on sample preparation  Sample treatments  Multiple steps during treatments  sample treatments up to 5h for each sample /batch of samples  Large amount of samples/aliquots  up to 10 different assays on 1 time point  Specific conditions  Time consuming treatment schedules  New processes  new techniques  Implementation new techniques  Need for training, specific qualifications  Running pilot studies evolution
  5. 5. 5 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015 SAMPLES WITHIN CLINICAL TRIALS  Lab manuals getting more specific/demanding  Specific conditions/requests  Timelines to centrifugation  Timelines after centrifugation  Timelines to storage  Storage conditions  Matrix used  Additional handling steps  …. All this makes it more challeging to maintain good sample quality and to plan resources
  6. 6. 6 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015 WHAT’S ON THE OTHER END? Why are all these parameters set? How do we get to these (more complex) sample treatments? What are the thoughts/reasoning behind it? How is it proven to be effective? How will information passed by from lab to site?
  7. 7. 7 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015 SETTING THE RIGHT PARAMETERS  Source :” The effects of anticoagulant choice and sample processing time on hematologic values of juvenile whooping cranes” (Joan Maurer,Betsy Reichenberg, Cristin Kelly,Barry K. Hartup)  Case study describes collection blood and the outcome with following factors  2 anti- Coagulants used (K3 EDTA and LiHE)  Slides made immediatly versus 4-6h delay  Questions  Does the anti coagulatant has an impact on results?  Does the processing time have an impact on results?  Is there any correlation of factors between anti-Coalgulant and/or sample processing time? 1
  8. 8. 8 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015 SETTING THE RIGHT PARAMETERS  The total granulocyte concentration(heterophils and eosinophils; H/E concentration) of each of the divided samples
  9. 9. 9 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015 SETTING THE RIGHT PARAMETERS  The relative (%) leukocyte counts of each of the divided samples
  10. 10. 10 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015 SETTING THE RIGHT PARAMETERS  In this specific case study no effect has been seen on results depending on your anti-coagulant if an immediate sample processing was feasible.  However when having a time delay (sample processing) this have an impact Validation of techniques on specific parameters is key to check if : • goals are reached • final results provided are fully “appropriate and correct” to analysis demands and results
  11. 11. 11 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015 VALIDATION – TIME & RESOURCE  Part 1 : Method Implementation and qualification  Set up and testing of PBMC protocol for preparation and testing  Testing of PBMC stimulation procedure  Testing labelling procedures  Lysis, fixation, permeabilization buffer selection  Acquisition and analysis templates/gating strategy  Preliminary testing of method reproducibility BioanalyticalLab 1month 2
  12. 12. 12 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015  Part 2 : In-vitro feasibility testing of the effect of product on CD4 Th1/Th2 and Treg response  Set-up of culture conditions and stimulation (reagents, stimulus, duration of culture, of stimulation)  Dose- and time effect of product (n= up to 6 subjects)  Test in-vitro effect on both CD4 Th1/ Th2 and Treg responses  Culture conditions in duplicate  FACS testing in duplicate  Data processing and statistical analysis BioanalyticalLab 1month VALIDATION – TIME & RESOURCE
  13. 13. 13 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015  Part 3 : Validation of a FACS method for analysis of CD4 Th1/ Th2 subset (CD3, CD4, IFN-Gamma, IL-4) and T Regulatory (CD3, CD4, CD25, FoxP3, CD127)  Sensitivity  Reproducibility: • Between replicates; • Between runs ; • Between analysts; • Between donors; • Between two FACS systems.  Stability testing (e.g. storage of PBMC and effect of cryopreservation, stability of reagents)  Robustness BioanalyticalLab 1month VALIDATION – TIME & RESOURCE
  14. 14. 14 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015  Part 4 : transition of the method to the clinical site  Providing procedure  Providing training • Handling steps • Conditions • Go’s don’t go’s  Running pilot study  qualification staff • Between replicates Analyst evaluation • Between analysts  method/training validation  Reviewing results  Running clinical trial ClinicalSite 1month VALIDATION – TIME & RESOURCE
  15. 15. 15 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015 VALIDATION – TIME & RESOURCE  Part 5 : Testing of CD4 Th1/ Th2 subset (CD3, CD4, IFN-g, IL-4) and T Regulatory (CD3, CD4, CD25, FoxP3, CD127) in clinical study samples  PBMC stimulation / 230 samples  CD4 Th1/ Th2 (CD3, CD4, IFN-Gamma, IL-4) FACS analysis/ 230 samples  T Regulatory (CD3, CD4, CD25, FoxP3, CD127) FACS analysis/ 230 samples BioanalyticalLab Xmonths
  16. 16. 16 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015 OTHER EXAMPLES  Urine collections : adding of additional products as Tween or BSA to avoid interference on tubes  Determination of Cytokines : use of a non standard blood collection tube such as Tru Culture tubes  Sputum induction: effect of using Sputolysin during handling on end parameters  Use of matrix : effect of presence of binding factors on specific compounds/ parameters  Storage conditions : use of snapfreezing samples, storage at -20°C or -70°C  …
  17. 17. 17 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015 CONCLUSION  Choose wise on parameters such as  Sampling tubes (anti coagulant)  Conditions  Sample processing times  Methods  …..  Validation of techniques is crucial  Implementation  time consuming  Communication/training between bioanalytical lab and site is key to :  get good final results  understand potential pitt falls for bioanalytical outcome
  18. 18. 18 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015 HOW DO WE ASSIST YOU IN THIS PROCESS?  Validation and choosing the right method is key for good results  How do we achieve a good technique to deliver very good Data when running a clinical trial?  Specialists on the bioanalytical part, Set up/validation techniques  Specialists on the site part  excecution  Running pilot studies between site and the BAN lab • Handling of samples? • Conditions? • Experience • Communication flow
  19. 19. 19 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015 PHARMACOLOGY SYNERGIES - FROM LAB TO CLINICAL (AND VICE VERSA) -  A Clinical Pharmacology Unit with  GMP pharmacy  Class II GCP laboratory  Fahmp & mec agreement  Mass Spectrometry & Immunoassays Experts  4 GLP/GMP Bioanalytical Laboratories  25 years experience  700 methods validated  31 LC-MS/MS  Services for small and large molecule testing in TK, PK and PD  Online clinical samples dosing with CPUs  Discovery biomarkers translated in clinical research  Immune function testing • Immunogenicity, flow cytometry, cytokine multiplexed ELISA  Biopharmaceuticals - Cell characterization  Metabolite profiling and mass balance studies (14C-labelled drug)
  20. 20. 20 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015 Life Science Services Pillu Haiko Head Technical Operations SGS Belgium NV Phone: + 32 3 217 25 77 Clinical Pharmacology Unit Fax: +32 (0) 3 217 25 81 Lange Beeldekensstraat 267 E-mail : haiko.pillu@sgs.com 2060 Antwerpen Belgium Web : www.sgs.com/lifescience THANK YOU FOR YOUR ATTENTION + 41 22 739 9548 + 1 866 SGS 5003 + 65 637 90 111 + 33 1 53 78 18 79 + 1 877 677 2667 + 33 1 41 24 87 87
  21. 21. 21 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015 QUESTIONS ?
  22. 22. 22 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015

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